Immunosuppression and debilitating illnesses are occasionally associated with multifocal brain lesions of Acanthamoebiasis, an encephalitis distinct from the acute, water-sport related meningoencephalitis caused by Naegleria fowler. A 38-year-old man with a renal transplant two and one-half years before his final illness developed pneumonia due to Legionella micdadei. Candida albicans was isolated from sputum and cytomegalovirus was found in lung and liver biopsies. He had continuous corticosteroids, broad spectrum antibiotics, and immunosuppressive therapies. Coma developed and computerized tomography of the head revealed multifocal areas of decreased density, interpreted as cerebral abscesses. Brain biopsy demonstrated encephalitis and amoebae (Acanthamoeba castellanii). Four days after brain biopsy, he died and multifocal hemorrhagic lesions were found in the cerebral hemispheres, brainstem, and cerebellum. This case supports the hypothesis that Acanthamoebiasis is an opportunistic infection.